Department of Animal Science, College of Animal Science and Technology, Anhui Science and Technology University, Bengbu, China.
Anim Sci J. 2011 Apr;82(2):244-50. doi: 10.1111/j.1740-0929.2010.00832.x. Epub 2011 Feb 24.
Vascular endothelial growth factor (VEGF)-dependent angiogenesis is crucial for corpus leteum formation and their functional maintenance in mammalian ovaries. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1α-mediated transcriptional activation contributes to the increased expression of VEGF gene in response to hypoxia in the bovine developing luteal cells (LCs). By real-time RT-PCR analysis, VEGF messenger RNA (mRNA) expression was found to significantly increase under hypoxia or treatment with desferrioxamine (DFX), cobalt chloride (CoCl(2)) or even N-carbobenzoxyl-L-leucinyl-L-leucinyl-L-norvalinal (MG-132), while these increased VEGF mRNA expressions could also be blocked by ferrous ammonium sulfate (FAS) or cis-element oligodeoxynucleotide (dsODN) transfection under hypoxia. Further analysis also found that these changes of VEGF mRNA were consistent with HIF-1α expression or HIF-1 activity. Taken together, our results indicate that VEGF is transcriptionally activated by hypoxia through HIF-1α-mediated mechanisms in LCs. This hypoxia-induced transcriptional activation may be one of the important mechanisms mediating the increase of VEGF expression in developing LCs during mammalian corpus leteum formation.
血管内皮生长因子 (VEGF) 依赖性血管生成对于哺乳动物卵巢黄体形成及其功能维持至关重要。本研究旨在验证假设，即缺氧诱导因子 (HIF)-1α介导的转录激活有助于牛黄体细胞 (LC) 对缺氧的反应中 VEGF 基因的表达增加。通过实时 RT-PCR 分析，发现 VEGF 信使 RNA (mRNA) 表达在缺氧或用去铁胺 (DFX)、氯化钴 (CoCl(2)) 甚至 N-羰苄氧羰基-L-亮氨酰-L-亮氨酰-L-正缬氨酸 (MG-132) 处理下显著增加，而这些增加的 VEGF mRNA 表达也可以被缺氧下的硫酸亚铁铵 (FAS) 或顺式元件寡脱氧核苷酸 (dsODN) 转染阻断。进一步分析还发现，VEGF mRNA 的这些变化与 HIF-1α 表达或 HIF-1 活性一致。总之，我们的结果表明，LC 中通过 HIF-1α 介导的机制，VEGF 通过缺氧被转录激活。这种缺氧诱导的转录激活可能是哺乳动物黄体形成过程中发育中的黄体细胞中 VEGF 表达增加的重要机制之一。
